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Glomerular basement membrane diseases - Essay Example

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It consists of a central thick electro-dense layer known as lamina densa surrounded by 2 thin peripheral layers, the lamina rara interna and lamina…
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Glomerular basement membrane diseases
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NORMAL GBM. LEFT - a single glomerulus. There are one million of these in each kidney. RIGHT - a close up of the GBM (G) around part of one tiny blood vessel in a glomerulus (red circle in left hand diagram) Alport syndrome is the second most common inherited cause of renal failure (Turner, 2006). The disorder involves basement membranes of the kidneys and sometimes even the cochlea and the eye (Devarajan, 2008). It occurs as a result of mutations in type IV collagen genes. There are different modes of inheritance of this disease.

The commonest is X-linked which is seen in 80% of the cases. Autosomal recessive inheritance is seen in 15 % of the cases and autosomal dominant inheritance is noted in 5% of the patients with Alport syndrome. Presence of 3 of the following 4 clinical presentation is necessary to arrive at a diagnosis of Alport syndrome (Devarajan, 2008). 50-80% of patients with X-linked Alport syndrome have mutations in the COL4A5 gene. Some may even have mutations of COL4A6 along with COL4A5 gene (Devarajan, 2008).

There are several hundred mutations of this gene which account for most cases of X-linked Alport syndrome. These mutations include missense mutations, splice-site mutations, and small deletions. The most common mutation is substitution for glycine in the collagenous domain of the a5 (IV) chain by a bulky amino acid. This mutation results in protein-folding abnormalities. Other mutations result in interchain association and formation of the collagen network due to premature termination of protein translation and loss of the carboxy-terminal NC1 domain.

Patients with autosomal recessive and autosomal dominant Alport syndrome have mutations in COL4A3 and COL4A4 (Devarajan, 2008). Most patients of Alport syndrome present during the first 2 decades of life with persistent microscopic hematuria and episodic gross hematuria. The common X-linked form of Alport syndrome leading to ESRD predominantly affects male

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